Introduction Diabetes mellitus is a global public health emergency in the twenty-first century. Diabetes patients who had to adhere to good self-care recommendation can prevent the complication associated with diabetes mellitus. Self-care management of diabetes mellitus in Sub-Saharan Africa was poor including Ethiopia. The aim of this study was to assess factors influencing diabetes self-care practice among type 2 diabetes patients at Debre Tabor General Hospital, Northwest Ethiopia diabetes clinic follow up unit. Methods An institutional based cross-sectional survey was conducted on systematically sampled 405 type 2 diabetes patients at Debre Tabor General Hospital diabetes clinic from June 02/2018 to June 30/2018. Bivariate and multivariable logistic regression was fitted to identify independent predictors of diabetes self-care practice. A p value of less than 0.05 was used to declare statistical significance. Results A total of 385 type 2 diabetes patients participated with a response rate of 95%, of which 243 (63.1%) study participants had good self-care practice. The mean ± SD age of the respondents and the duration of diagnosed for diabetes mellitus was 52.28 ± 12.45 and 5.09 ± 3.80 years respectively. Type 2 diabetes patients who had a glucometer at home (AOR = 7.82 CI (3.24, 18.87)), getting a diabetes education (AOR = 2.65 CI (1.44, 4.89)), and having social support (AOR = 2.72 CI (1.66, 4.47)) were statistically associated with good self-care practice. Conclusion Despite, the importance of diabetes self-care practice for the management of diabetes and preventing its complications, a significant number of type 2 diabetes patients had poor diabetes self-care practice. So, to enhance this poor practice of diabetes self-care, provision of diabetes self-care education and counseling on self-monitoring blood glucose should be promote by health care providers during their follow up.